Factor can accelerate recovery after HSCT

Stem cells

The administration of prostaglandin E2 (PGE2) can lead to quicker hematopoietic recovery after hematopoietic stem cell transplant (HSCT), according to results observed in a murine study. 

Researchers at the University of Rochester in New York found that PGE2 altered the bone microarchitecture, had a regulatory effect on HSCs in the absence of injury, and preferentially expanded short-term HSCs without impacting long-term HSCs.  

Laura M. Calvi, MD, and colleagues knew that PGE2 affects osteoblasts and osteoclasts, expands HSCs in vitro, and affects differentiation of hematopoietic progenitors. So the team theorized that PGE2 could expand HSCs in vivo by affecting both HSCs and their microenvironment.

To test their theory, the researchers injected test mice with PGE2 at 6 mg per kg of body weight and injected control mice with the same amount of a solution of 4% Ethanol in molecular grade water. Mice received injections twice daily for 16 days.

Twenty-four hours after the final injection, Dr Calvi and colleagues harvested the hindlimbs of test and control mice. For each mouse, the team used one limb for bone marrow harvest and the other for analysis by micro-CT and histology. 

Histologic analysis of the distal femur revealed disrupted trabeculae with increased trabecular spacing in mice treated with PGE2. Micro-CT scanning also showed increased trabecular spacing and decreased numbers of trabeculae in the metaphyseal areas of femora and tibiae in the treated mice. So the researchers concluded that PGE2 has a significant affect on bone microarchitecture.

The team next assessed the hematopoietic effects of PGE2. They performed peripheral blood cell counts and determined the number of bone marrow hematopoietic progenitors but found that neither differed between test and control mice. However, there was a significant increase in lineage- Sca-1+ c-kit+ (LSK) bone marrow cells following treatment with PGE2, and this effect was dose-dependent.

So Dr Calvi and colleagues decided to take a closer look at LSK cells to determine the effect of PGE2 on long-term HSCs, short-term HSCs, and multipotent progenitors. Flow cytometric analysis revealed that PGE2 does not increase long-term HSCs, but it does expand short-term HSC populations.

Taking this finding a step further, the researchers transplanted the treated and untreated bone marrow cells into lethally irradiated wild-type mice. Eight days after transplant, mice who received PGE2-treated cells had significantly more spleen colonies than mice transplanted with control cells. However, from day 10 to day 12 after transplant, there was no difference in the number of spleen colonies between the 2 groups of mice.

The researchers’ last step was to determine the effect of PGE2 on hematopoietic engraftment. PGE2 led to greater reconstitution in the myeloid and B-cell compartments at 2, 3, and 4 weeks after transplant. However, this early increase in engraftment was lost, beginning at 6 weeks after transplant.

Dr Calvi and colleagues said these results indicate that PGE2 preferentially expands HSCs with limited self-renewal capability, and it can therefore be used to accelerate hematopoietic recovery following transplant. The team reported these findings in the early online edition of Blood on September 2.